1. Field of the Invention
This invention relates to a method for reducing the use of cocaine in animals, including humans, by the administration of valproic acid.
2. Description of the Related Art
Treatment for cocaine abuse has been largely ineffective, based on cocaine relapse rates. Depending on the level of habituation or dependence, and prognostic features, i.e. job, marital status, additional psychopathology, etc., upwards of 60-100% of cocaine dependent patients relapse within the first 12 months no matter how high their motivation. For most, this relapse rate is due to an overwhelming "craving" for the drug (Dackis et al, Arch. Gen. Psychiatry, 44: 298-9, 1987).
There have been a number of studies in which various pharmacologic agents have been used to treat cocaine dependence: Bromocriptine, bromocriptine-desipramine combination, amantadine, imipramine, L. L.tyrosine and L.tryptophan in combination, and desipramine. Both amantadine and bromocriptine have been used primarily to treat the cocaine withdrawal syndrome but long-term studies using either have not yet been conducted.
The tricyclic antidepressant, desipramine, has been the most extensively studied of pharmacologic agents. Maintenance with desipramine for 3-4 weeks is required before any significant decrease in craving occurs.
Biological hypotheses regarding cocaine craving have focused on the dopaminergic reward pathways. Two of the more recent theories have suggested that craving is at least in part due to a "down" regulation of the dopamine reward system following chronic cocaine abuse. Instead, the inventor postulates that cocaine craving involves an alternate specific neurophysiological mechanism related to kindling.
The inventor filed U.S. patent application Ser. No. 07/373,385, filed June 25, 1989, on a method for treating cocaine use with carbamazepine. That application is to issue on July 2, 1991 as U.S. Pat. No. 5,028,611, the disclosure of which is incorporated herein by reference. Further papers concerning the use of carbamazepine by the inventor include Halikas et al, "Carbamazepine for Cocaine Addiction?", The Lancet, Mar. 18, 1989, pp. 623-624; Halikas et al, "Reduction of Cocaine Use Among Methadone Maintenance Patients Using Concurrent Carbamazepine Maintenance", Annals of Clinical Psychiatry, 1990, 2: 3-6; and Halikas et al, "A Possible Neurophysiological Basis of Cocaine Craving", Annals of Clinical Psychiatry, 1990, 2: 79-83.
U.S. Pat. No. 4,942,182 to Post et al, which issused July 17, 1990, involves blocking "toxic effects" and "reinforcing effects" of cocaine in rats using carbamazepine. Post has also published an article in The Journal of Clinical Psychiatry, "Introduction: Emerging Perspectives on Valproate in Affective Disorders" (1989); 50(3)(Sec. 2): 3-9.
The art described in this section is not intended to constitute an admission that any patent, publication or other information referred to herein is "prior art" with respect to this invention, unless specifically designated as such. In addition, this section should not be constructed to mean that a search has been made or that no other pertinent information as defined in 37 C.F.R. .sctn.1.56(a) exists.